title: Increased skeletal muscle-specific microRNA in the blood of patients with COPD.
abstract: BACKGROUND
  Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) carries a poor prognosis, therefore a non-invasive marker of this process could be useful. Reduced expression of muscle-specific microRNA (myomiRs) in quadriceps muscle in patients with COPD is associated with skeletal muscle weakness and changes in muscle fibre composition. Circulating exosomal miRNAs can be measured in blood, making them candidate biomarkers of biopsy phenotype. To determine whether plasma myomiR levels were associated with fibre size or fibre proportion, we measured myomiRs in plasma from patients with COPD and healthy controls.
  
  
  RESULTS
  103 patients with COPD and 25 age-matched controls were studied. Muscle-specific miRNA was elevated in the plasma of patients with COPD and showed distinct patterns. Specifically, miR-1 was inversely associated with fat-free mass in the cohort, whereas levels of miR-499 were more directly associated with strength and quadriceps type I fibre proportion. Two miRs not restricted to muscle in origin (miR-16 and miR-122) did not differ between patients and controls. Plasma miR-499 was also associated with muscle nuclear factor κB p50 but not p65 in patients with early COPD whereas plasma inflammatory cytokines were associated with miR-206 in patients with more advanced disease.
  
  
  CONCLUSIONS
  Plasma levels of individual myomiRs are altered in patients with COPD but alone do not predict muscle fibre size or proportion. Our findings are consistent with an increase in muscle wasting and turnover associated with the development of skeletal muscle dysfunction and fibre-type shift in patients with stable COPD.
authors.affiliation: Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, , London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Donaldson
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Natanek
authors.forename: Amy
authors.initials: A
authors.lastname: Lewis
authors.forename: William D-C
authors.initials: WD
authors.lastname: Man
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kemp
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D018657:Muscle Fibers, Slow-Twitch / Q000473:pathology; D053580:Muscle Strength; D018908:Muscle Weakness / Q000097:blood* / Q000209:etiology / Q000473:pathology*; D052002:NF-kappa B p50 Subunit / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; C544547:MIRN1 microRNA, human; C546087:MIRN206 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA
keywords: COPD Pathology; Exercise; Systemic disease and lungs